The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses.
GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed that GABA(B(1a,2)) receptors are more abundant than GABA(B(1b,2)) receptors at glutamatergic terminals. Accordingly, it was found that GABA(B(1a,2)) receptors are more efficient than GABA(B(1b,2)) receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen. Here, we used a combination of genetic, ultrastructural and electrophysiological approaches to analyze to what extent GABA(B(1a,2)) and GABA(B(1b,2)) receptors inhibit glutamate release in response to physiological activation. We first show that at hippocampal mossy fiber (MF)-CA3 pyramidal neuron synapses more GABA(B1a) than GABA(B1b) protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations >or=1 microm, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABA(B(1a,2)) receptors contribute to presynaptic inhibition. Remarkably, exclusively GABA(B(1a,2)) receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABA(B(1a,2)) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.


Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays.
Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect. Sandwich immunoassays and specimen handling procedures were developed and validated for quantifying full-length MET and its key phosphospecies (pMET) in core tumor biopsies. MET was captured using an antibody to the extracellular domain and then probed using antibodies to its C-terminus (full-length) and epitopes containing pY1234/1235, pY1235, and pY1356. Using pMET:MET ratios as assay endpoints, MET inhibitor pharmacodynamics were characterized in MET-amplified and -compensated (VEGFR blockade) models. By limiting cold ischemia time to less than two minutes, the pharmacodynamic effects of the MET inhibitors PHA665752 and PF02341066 (crizotinib) were quantifiable using core needle biopsies of human gastric carcinoma xenografts (GTL-16 and SNU5). One dose decreased pY1234/1235 MET:MET, pY1235-MET:MET, and pY1356-MET:MET ratios by 60% to 80% within 4 hours, but this effect was not fully sustained despite continued daily dosing. VEGFR blockade by pazopanib increased pY1235-MET:MET and pY1356-MET:MET ratios, which was reversed by tivantinib. Full-length MET was quantifiable in 5 of 5 core needle samples obtained from a resected hereditary papillary renal carcinoma, but the levels of pMET species were near the assay lower limit of quantitation. These validated immunoassays for pharmacodynamic biomarkers of MET signaling are suitable for studying MET responses in amplified cancers as well as compensatory responses to VEGFR blockade. Incorporating pharmacodynamic biomarker studies into clinical trials of MET inhibitors could provide critical proof of mechanism and proof of concept for the field. Clin Cancer Res; 22(14); 3683-94. ©2016 AACR.


Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover.
Emerging viral diseases are a major threat to global health, and nearly two-thirds of emerging human infectious diseases are zoonotic. Most of the human epidemics and pandemics were caused by the spillover of viruses from wild mammals. Viruses that infect humans and a wide range of animals have historically caused devastating epidemics and pandemics. An in-depth understanding of the mechanisms of viral emergence and zoonotic spillover is still lacking. Receptors are major determinants of host susceptibility to viruses. Animal species sharing host cell receptors that support the binding of multiple viruses can play a key role in virus spillover and the emergence of novel viruses and their variants. Sialic acids (SAs), which are linked to glycoproteins and ganglioside serve as receptors for several human and animal viruses. In particular, influenza and coronaviruses, which represent two of the most important zoonotic threats, use SAs as cellular entry receptors. This is a comprehensive review of our current knowledge of SA receptor distribution among animal species and the range of viruses that use SAs as receptors. SA receptor tropism and the predicted natural susceptibility to viruses can inform targeted surveillance of domestic and wild animals to prevent the future emergence of zoonotic viruses.


Conditioned medium increases the polyploid cell composition of bovine somatic cell nuclear-transferred blastocysts.
The effects of bovine cumulus cell-conditioned medium on cloned bovine embryonic development and subsequent chromosome complement were examined using an air-dry procedure. Conditioned media were prepared using CR1aa supplemented with either fetal bovine serum (FBS) or bovine serum albumin (BSA). Nuclear-transferred embryos were reconstructed with nuclei from cumulus cells. Similar cleavage, morula, and blastocyst development was observed in conditioned media groups compared with the co-culture group. No differences (P > 0.05) were observed in the composition of blastocyst chromosomes after co-culture in different media, either with or without starvation of donor cells. The overall diploid blastocyst rate ranged from 75% to 84%. Chromosomal complement of blastocysts, however, was very different between conditioned medium and co-culture treatments. Overall incidence of chromosomal anomalies was 40% in conditioned medium, which was significantly higher (P < 0.001) than the co-culture group (20%). Moreover, a higher incidence (P < 0.05) of chromosomally abnormal blastocysts (41.5%) was observed after culture with FBS-containing conditioned medium than those cultured in BSA-containing conditioned medium (31.4%). No diploid improvement was observed after exchange of the culture system from conditioned medium to co-culture, or from co-culture to conditioned medium after the first 72 h of culture. The results of this study also indicated that the overall cell number was much lower (P < 0.01) in blastocysts with chromosomal abnormalities than those with a normal diploid state. We have concluded that medium conditioned with bovine cumulus cells increases the incidence of chromosomal anomalies in nuclear reconstructed embryos.


Hearing loss in low-birth-weight infants.
The hearing of 98 perinatal intensive care survivors with a mean birth weight of 1,540 g was assessed at a mean age of 6 1/2 years. They represented 73% of the long-term survivors with birth weights of 1,800 g or less who had been cared for in our neonatal unit during the three-year period 1971 through 1973. Nine of the 98 infants had sensorineural hearing loss, and 14 had exudative otitis media. During their neonatal period, the infants with hearing loss experienced more frequent apneic attacks, hyperbilirubinemia (serum bilirubin level, greater than 14 mg/dL), and hypothermia compared with their healthy counterparts. There was no evidence that the duration of stay in the incubator or the use of stay in the incubator or the use of ototoxic drugs had affected the hearing of these low-birth-weight infants.


Correlating brain blood oxygenation level dependent (BOLD) fractal dimension mapping with magnetic resonance spectroscopy (MRS) in Alzheimer's disease.
To correlate temporal fractal structure of resting state blood oxygen level dependent (rsBOLD) functional magnetic resonance imaging (fMRI) with in vivo proton magnetic resonance spectroscopy ((1)H-MRS), in Alzheimer's disease (AD) and healthy age-matched normal controls (NC). High temporal resolution (4 Hz) rsBOLD signal and single voxel (left putamen) magnetic resonance spectroscopy data was acquired in 33 AD patients and 13 NC. The rsBOLD data was analyzed using two types of fractal dimension (FD) analysis based on relative dispersion and frequency power spectrum. Comparisons in FD were performed between AD and NC, and FD measures were correlated with (1)H-MRS findings. Temporal fractal analysis of rsBOLD, was able to differentiate AD from NC subjects (P = 0.03). Low FD correlated with markers of AD severity including decreased concentrations of N-acetyl aspartate (R = 0.44, P = 0.015) and increased myoinositol (mI) (R = -0.45, P = 0.012). Based on these results we suggest fractal analysis of rsBOLD could provide an early marker of AD.


Coherent perfect absorption in wedged organic thin films: a method to determine optical properties.
We investigate coherent perfect absorption in layered thin-film structures with organic small molecules as absorbing material. We focus on strongly asymmetric resonator structures, realized with a high-optical-quality dielectric-distributed Bragg reflector and a thermally evaporated wedged organic layer on top. The optical properties of these devices are systematically investigated by selective optical pumping and probing of the structure along the wedge. We show that phases and amplitudes of all waves and their balance relations can be tuned such that coherent perfect absorption is achieved, i.e., almost all incident radiation is absorbed within the thin organic layer. We show that such wedged structures on highly reflective dielectric mirrors can be used as a novel approach to measure optical dispersion relations of absorbing materials in a broad spectral range without requiring any specific a priori knowledge of the absorbing film.


Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos?
What is the impact of ovarian response on cumulative live birth rates (LBR) following utilization of all fresh and frozen embryos in women undergoing their first ovarian stimulation cycle, planned to undergo single embryo transfer (SET). Cumulative LBR significantly increases with the number of oocytes retrieved. Several studies have addressed the issue of the optimal number of oocytes retrieved following controlled ovarian stimulation (COS) for IVF/ICSI and demonstrated that ovarian response is independently related to LBR following IVF/ICSI. The vast majority of studies pertained only to the outcome of the fresh IVF cycle and did not evaluate the cumulative LBR following the transfer of all fresh and frozen-thawed embryos after a single ovarian stimulation, which is the most meaningful outcome for the infertile patient. This study is a large cohort analysis of retrospective data from January 2009 to December 2013 in a tertiary medical centre, at the Centre for Reproductive Medicine at the University Hospital of Brussels. This study included 1099 eligible consecutive women 18-40 years old undergoing their first IVF cycle and planned to undergo SET in their fresh cycle. All patients were treated with a conventional starting gonadotrophin dose of 150-225 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. Vitrification was used as cryopreservation method. To evaluate the impact of oocyte yield on fresh LBR and on cumulative LBR after utilization of all cryopreserved embryos, patients were categorized into four groups according to the number of oocytes retrieved: 1-3 (Group A), 4-9 (Group B), 10-15 (Group C) or >15 oocytes (Group D). Regarding LBR in the fresh IVF/ICSI cycles, unadjusted results did not show any significant difference when comparing either high (>15 oocytes) versus normal (10-15 oocytes) (P = 0.65), or normal (10-15) versus suboptimal (4-9 oocytes) responders (P = 0.2). LBR in the fresh cycles were significantly higher (P < 0.05) in high, normal and suboptimal responders when compared with the low ovarian responder group (1-3 oocytes). Moderate-severe ovarian hyperstimulation syndrome occurred in 11 out of 1099 patients (1%). The cumulative LBR significantly increased with the number of oocytes retrieved (χ(2) test for trend P < 0.001). High responders (>15 oocytes) demonstrated a significantly higher LBR not only versus poor (0-3 oocytes) (P < 0.001) and suboptimal (4-9) responders (P < 0.001), but also versus women with normal (10-15) ovarian response (P = 0.014). Finally, although suboptimal responders had a better outcome compared with poor ovarian responders (P = 0.002), this group had a significantly lower cumulative LBR compared with normal ovarian responders (P = 0.02). Multivariate logistic regression analysis showed that the ovarian response category remained an independent predictive factor (P < 0.001) for cumulative LBR. This is a cohort analysis based on retrospective data collection. Despite our robust methodological approach, the presence of biases related to retrospective design cannot be excluded. High responders may inherently have had a better prognosis. In addition, we cannot provide any guidance for patients undergoing either multiple embryo transfers or treated with higher gonadotrophin doses. Women undergoing COS for their first IVF/ICSI cycle and SET should be informed that, although the number of oocytes retrieved does not affect LBR in the fresh cycle, the higher the oocyte yield, the higher the probability to achieve a live birth after utilization of all cryopreserved embryos. Large cohort studies are needed in order to confirm our results of cumulative LBR in different ovarian stimulation settings with higher stimulation doses. No external funding was used for this study. No conflicts of interest are declared.


Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival.
To evaluate how implementation of the 2003 American Joint Committee on Cancer (AJCC) staging system will affect stage-specific survival of breast cancer patients. Records of 1,350 patients treated on sequential institutional protocols with mastectomy and adjuvant doxorubicin-based chemotherapy were reviewed. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging criteria. Overall stage-specific survival (OS) was calculated using the Kaplan-Meier method, and hypothetical differences were compared by the log-rank test. Six hundred five of 1,087 patients with stage II disease according to the 1988 classification system had stage II disease according to the 2003 system. The 10-year OS for patients with stage II disease was significantly improved using the 2003 system (76% [2003] v 65% [1988]; P <.0001). Two hundred eighty-nine of 633 patients with stage IIb disease using the 1988 system were stage IIb with the 2003 system, and 10-year OS was 58% (1988) versus 70% (2003; P =.003). The number of patients with stage III disease increased from 207 (1988) to 443 (2003), and the 10-year OS changed from 45% (1988) to 50% (2003; P =.077). Most of this difference resulted from changes within stage IIIa: OS, 45% (1988) versus 59% (2003; P <.0001). Stage reclassification using the new AJCC staging system for breast cancer will result in significant changes in reported outcome by stage. It is imperative that careful attention is devoted to this effect so that accurate conclusions regarding the efficacy of new treatment strategies can be drawn.


Isolated hepatic perfusion for lapine liver metastases: impact of hyperthermia on permeability of tumor neovasculature.
Hyperthermic isolated hepatic perfusion (IHP) has been shown to cause significant regression of advanced unresectable liver metastases in patients. Although there are different agents and treatment modalities used in IHP, the contribution of perfusion hyperthermia is unknown. A large animal model of unresectable liver metastases and a technical standard for IHP in this model were established. This model was used to assess the effects of hyperthermia on vascular permeability of tumors and normal liver tissue during IHP. Sixty-five New Zealand White rabbits were used in a series of experiments. Disseminated liver tumors were established by direct injection of 1 x 10(6) VX-2 cells into the portal vein by laparotomy in anesthetized animals. Several surgical perfusion techniques were explored to determine a reliable and reproducible IHP model. Vascular permeability in tumor versus liver was then assessed with Evan's Blue labeled bovine albumin under normothermic (tissue temperature 36.5 degrees C +/- 0.5 degree C), moderate hyperthermic (39 degrees C +/- 0.5 degree C), or severe hyperthermic (41 degrees C +/- 0.5 degree C) conditions. Tumor model and perfusion techniques were successfully established with inflow through the portal vein and outflow through an isolated segment of the inferior vena cava. A gravity driven perfusion circuit with stable perfusion parameters and complete vascular isolation was used. Vascular permeability was higher in tumor than in normal tissues (P = .03) at all time points during IHP. Hyperthermia resulted in a significant (up to 5-fold) increase in permeability of neovasculature; when severe hyperthermia was used, tumor vascular permeability was increased even more than normal liver permeability (P = .01). The VX-2/New Zealand White rabbit system can be used as a reproducible large-animal model for IHP of unresectable liver metastases. It can be used to characterize the contribution and mechanism of action of different treatment parameters used in IHP. Hyperthermia preferentially increases vascular permeability in tumors compared with liver tissue in a dose-dependent fashion, thus providing a mechanism for its presumed benefit during isolated organ perfusion.


Observation Services Linked With an Urgent Care Center in the Absence of an Emergency Department: An Innovative Mechanism to Initiate Efficient Health Care Delivery in the Aftermath of a Natural Disaster.
The emergency department (ED) of NYU Langone Medical Center was destroyed by Hurricane Sandy, contributing to a public health disaster in New York City. We evaluated hospital-based acute care provided through the establishment of an urgent care center with an associated ED-run observation service (EDOS) that operated in the absence of an ED during this disaster. We conducted a retrospective cohort study of all patients placed in an EDOS following a visit to an urgent care center during the 18 months of ED closure. We reviewed diagnoses, clinical protocols, selection criteria, and performance metrics. Of 55,723 urgent care center visits, 15,498 patients were hospitalized, and 3167 of all hospitalized patients (20.4%) were placed in the EDOS. A total of 2660 EDOS patients (84%) were discharged from the EDOS. The 8 most frequently utilized clinical protocols accounted for 76% of the EDOS volume. A diverse group of patients presenting to an urgent care center following the destruction of an ED by natural disaster can be cared for in an EDOS, regardless of association with a physical ED. An urgent care center with an associated EDOS can be implemented to provide patient care in a disaster situation. This may be useful when existing ED or hospital resources are compromised. (Disaster Med Public Health Preparedness. 2016;10:405-410).


The Link Between Neuroticism and Everyday Cognitive Failures is Mediated by Self-Reported Mindfulness Among College Students.
Neuroticism has been linked to an increased likelihood of cognitive failures, including episodes of inattentiveness, forgetfulness, or accidents causing difficulties in successfully executing everyday tasks and impacting health and quality of life. Cognitive failures associated with trait neuroticism can prompt some negative psychological outcomes and risky behaviors. Accumulating evidence shows that augmenting mindfulness can benefit cognitive health and general well-being. However, little is known regarding potential cognitive-behavioral pathways through which individual differences in trait neuroticism could influence the propensity to cognitive failures. Using a sample of 1003 undergraduate college students (females: n = 779) consisting of self-reported questionnaire data, we conducted correlational and mediational analyses to investigate the interrelationship between neuroticism, mindfulness, and cognitive failures. Higher neuroticism scores (females: r = -0.388, males: r = -0.390) and higher cognitive failures scores (females: r = -0.339, males: r = -0.407, p < .001) were significantly correlated with lower self-reported mindfulness scores. Mindfulness significantly mediated the relationship between neuroticism and cognitive failures (β = 0.50, 95%, CI: 0.37, 0.65). These findings indicate that higher mindfulness may help ameliorate negative effects of neuroticism on everyday cognitive failures. Future research will determine how college students may benefit from positive impact of mindfulness to improve their psychological and physical health.


The mating pilus of E. coli pED208 acts as a conduit for ssDNA during horizontal gene transfer.
Bacteria are constantly exchanging DNA, which constitutes horizontal gene transfer. While some of these occurs by a non-specific process called natural transformation, some occurs by a specific mating between a donor and a recipient cell. In specific conjugation, the mating pilus is extended from the donor cell to make contact with the recipient cell, but whether DNA is actually transferred through this pilus or by another mechanism involving the type IV secretion system complex without the pilus has been an open question. Using Escherichia coli, we show that DNA can be transferred through this pilus between a donor and a recipient cell that has not established a tight mating junction, providing a new picture for the role of this pilus.


Identification of side population cells in human hepatocellular carcinoma cell lines with stepwise metastatic potentials.
To identify the side population (SP) cells from four hepatocellular carcinoma (HCC) cell lines with stepwise metastatic potentials. SP cells were sorted from HCCLM3, MHCC97-H, MHCC97-L and Hep3B by flow cytometry, and then analyzed by differentiation study, clonogenic assay, chemoresistance study and tumorigenicity assay in vivo. The expression of ABCG(2) in SP cells was detected by immunocytochemistry, western blotting and real-time quantitative PCR, respectively. There was significant difference in SP proportion among HCCLM3, MHCC97-H, MHCC97-L and Hep3B (28.7 +/- 1.6%, 14.5 +/- 0.6%, 4.2 +/- 0.4%, 0.9 +/- 0.1%, respectively, P < 0.01). All the SP cells showed similar characteristics of self-renewal, high clonogenicity, remarkable chemo-resistance and high expression of ABCG(2). As low as 2,000 SP cells could initiate tumors in non-obese diabetic/severe combined immunodeficiency mice successfully. SP cells purified from HCC cell lines harbors cancer stem cell-like properties, and may be related to the metastatic potentials and therapeutic-resistance of HCC.


An examination of generalized anxiety disorder and dysthymia utilizing the Rorschach inkblot method.
This study examined transdiagnostic features of generalized anxiety disorder (GAD) and dysthymia in an outpatient clinical sample. Fifteen patients who met DSM-IV criteria for GAD and twenty-one patients who met DSM-IV criteria for dysthymia but who did not have comorbid anxiety disorder were evaluated utilizing the Rorschach. Salient clinical variables were then compared. Results showed that patients with GAD scored significantly higher on variables related to cognitive agitation and a desire/need for external soothing. In addition, there was a trend for patients with GAD to produce higher scores on a measure of ruminative focus on negative aspects of the self. Thus, not surprisingly, GAD patients' experienced more distress than the dysthymic patients. The implications of these findings are discussed with regards to better understanding the shared and distinct features of GAD and dysthymia.


Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.
Colorectal cancer (CRC) is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU) is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα), an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy. ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS) and thymidine kinase (TK1) levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action. Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.


Efficacy of human immunoglobulin and penicillin G in treatment of experimental group B streptococcal infection.
In an effort to develop more effective therapy for neonatal group B streptococcal infections, penicillin G and human immune serum globulin (ISG), alone and in combination, were evaluated for their therapeutic efficacy against experimental group B streptococcal bacteremia and meningitis in newborn rats. Infected rats received either penicillin G (200 mg/kg/day), ISG (2 g/kg) or penicillin G (200 mg/kg/day) + varying doses of ISG (0.25 to 2 g/kg). All animals receiving ISG alone died; otherwise, mortality rates did not differ significantly (17-30%). Therapy with penicillin G alone and in combination with ISG was equally effective in completely eradicating group B streptococcal from blood and cerebrospinal fluid. However, combinations of penicillin G and ISG were significantly more beneficial than penicillin G alone, as shown by a significantly lower incidence of bacteremia at the end of 1 day of therapy and by greater opsonophagocytic activity in sera of animals receiving penicillin G + ISG. These findings indicate that administration of ISG in conjunction with penicillin G rapidly clears bacteria from blood, suggesting that ISG may be a useful adjunct to antimicrobial therapy of neonatal group B streptococcal disease.


How to Begin a Quality Improvement Project.
Quality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.


Smart sensing of cardiovascular physiological information from soles without direct skin contact.
This study proposes the development of a smart sensing measurement system using a mat-type sensor in order to obtain sole-electrocardiogram data from soles and toe-photoplethysmogram data from toes. In addition, the proposed measurement system can calculate pulse wave velocity from sole-ECG and toe-PPG. The subjective experiments revealed that the developed system can measure these parameters even when socks are being worn. Moreover, simultaneous measurements of systolic blood pressure and PWV determined by the developed system indicate a strong correlation was found between SBP and PWV. Therefore, this system can detect cardiovascular diseases or symptoms of common diseases and suggests the possibility to estimate the temporal changes in SBP without required compression using cuffs.


Elevated air movement enhances stomatal sensitivity to abscisic acid in leaves developed at high relative air humidity.
High relative air humidity (RH ≥ 85%) during growth leads to stomata malfunctioning, resulting in water stress when plants are transferred to conditions of high evaporative demand. In this study, we hypothesized that an elevated air movement (MOV) 24 h per day, during the whole period of leaf development would increase abscisic acid concentration ([ABA]) enhancing stomatal functioning. Pot rose 'Toril' was grown at moderate (61%) or high (92%) RH combined with a continuous low (0.08 m s(-1)) or high (0.92 m s(-1)) MOV. High MOV reduced stomatal pore length and aperture in plants developed at high RH. Moreover, stomatal function improved when high MOV-treated plants were subjected to leaflet desiccation and ABA feeding. Endogenous concentration of ABA and its metabolites in the leaves was reduced by 35% in high RH, but contrary to our hypothesis this concentration was not significantly affected by high MOV. Interestingly, in detached leaflets grown at high RH, high MOV increased stomatal sensitivity to ABA since the amount of exogenous ABA required to decrease the transpiration rate was significantly reduced. This is the first study to show that high MOV increases stomatal functionality in leaves developed at high RH by reducing the stomatal pore length and aperture and enhancing stomatal sensitivity to ABA rather than increasing leaf [ABA].


Phosphoinositide binding regulates alpha-actinin dynamics: mechanism for modulating cytoskeletal remodeling.
The active association-dissociation of dynamic protein-protein interactions is critical for the ability of the actin cytoskeleton to remodel. To determine the influence of phosphoinositide binding on the dynamic interaction of alpha-actinin with actin filaments and integrin adhesion receptors, fluorescence recovery after photobleaching (FRAP) microscopy was carried out comparing wild-type green fluorescent protein (GFP)-alpha-actinin and a GFP-alpha-actinin mutant with a decreased affinity for phosphoinositides (Fraley, T. S., Tran, T. C., Corgan, A. M., Nash, C. A., Hao, J., Critchley, D. R., and Greenwood, J. A. (2003) J. Biol. Chem. 278, 24039-24045). In fibroblasts, recovery of the mutant alpha-actinin protein was 2.2 times slower than the wild type along actin stress fibers and 1.5 times slower within focal adhesions. FRAP was also measured in U87MG glioblastoma cells, which have higher levels of 3-phosphorylated phosphoinositides. As expected, alpha-actinin turnover for both the stress fiber and focal adhesion populations was faster in U87MG cells compared with fibroblasts with recovery of the mutant protein slower than the wild type along actin stress fibers. To understand the influence of alpha-actinin turnover on the modulation of the actin cytoskeleton, wild-type or mutant alpha-actinin was co-expressed with constitutively active phosphoinositide (PI) 3-kinase. Co-expression with the alpha-actinin mutant inhibited actin reorganization with the appearance of enlarged alpha-actinin containing focal adhesions. These results demonstrate that the binding of phosphoinositides regulates the association-dissociation rate of alpha-actinin with actin filaments and integrin adhesion receptors and that the dynamics of alpha-actinin is important for PI 3-kinase-induced reorganization of the actin cytoskeleton. In conclusion, phosphoinositide regulation of alpha-actinin dynamics modulates the plasticity of the actin cytoskeleton influencing remodeling.


Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.
Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.


Associations between changes in physical activity and risk factors for coronary heart disease in a community-based sample of men and women: the Stanford Five-City Project.
Aerobic exercise training studies involving volunteers generally result in an improved cardiovascular risk factor profile. Little is known, however, about associations between physical activity change and risk factor change in a more representative sample, such as a community. This investigation evaluated correlations between a composite physical activity change score and change in cardiovascular risk factors from 1979 to 1985 in the cohort sample of the Stanford Five-City Project. Men (n = 380) and women (n = 427) between the ages of 18 and 74 years were evaluated for change in self-reported physical activity and change in total cholesterol, high density lipoprotein cholesterol (HDL cholesterol), systolic blood pressure, resting pulse rate, and body mass index (weight (kg)/height (m)2). For men, improvement in the composite physical activity score significantly correlated with an increase in HDL cholesterol (r = 0.14, p = 0.005) and decreases in body mass index (r = -0.16, p = 0.001) and estimated 10-year coronary heart disease risk score (r = -0.10, p = 0.056). For women, improvement in the physical activity score was associated with changes in HDL cholesterol (r = 0.11, p = 0.028) and resting pulse rate (r = -0.15, p = 0.001). These data demonstrate that an increase in physical activity over 5 years is favorably associated with changes in major cardiovascular disease risk factors in men and women and support the public health efficacy of community-wide promotion of physical activity.


Appointment completion in pediatric neurology telemedicine clinics serving underserved patients.
To determine whether telemedicine improves access to outpatient neurology care for underserved patients, we compared appointment completion between urban, in-person clinics and telemedicine clinics held in rural and underserved communities where neurology consultations are provided remotely. In this retrospective study, we identified patients scheduled for outpatient care from UCDH pediatric neurologists between January 1, 2009, and July 31, 2017, in person and by telemedicine. Demographic and clinical variables were abstracted from electronic medical records. We evaluated the association between consultation modality and visit completion in overall and matched samples using hierarchical multivariable logistic regression. We analyzed 13,311 in-person appointments by 3,831 patients and 1,158 telemedicine appointments by 381 patients. The average travel time to the site of care was 45.8 ± 52.1 minutes for the in-person cohort and 22.3 ± 22.7 minutes for the telemedicine cohort. Telemedicine sites were located at an average travel time of 217.1 ± 114.8 minutes from UCDH. Telemedicine patients were more likely to have nonprivate insurance, lower education, and lower household income. They had different diagnoses and fewer complex chronic conditions. Telemedicine visits were more likely to be completed than either "cancelled" or missed ("no show") compared with in-person visits (OR 1.57, 95% CI: 1.34-1.83; OR 1.66, 95% CI: 1.31-2.10 matched on travel time to the site of care; OR 2.22, 95% CI: 1.66-2.98 matched on travel time to UCDH). The use of telemedicine for outpatient pediatric neurology visits has high odds of completion and can serve as an equal adjunct to in-person clinic visits.


Heat capacity analysis of oxidized Escherichia coli thioredoxin fragments (1--73, 74--108) and their noncovalent complex. Evidence for the burial of apolar surface in protein unfolded states.
We have calculated the absolute heat capacities of fragments 1--73 (N fragment) and 74--108 (C fragment) from thioredoxin, their complex and the uncleaved protein, from the concentration dependence of the apparent heat capacities of the solutions determined by differential scanning calorimetry. We find that, while the absolute heat capacities of uncleaved, unfolded thioredoxin and the C fragment are in good agreement with the theoretical values expected for fully solvated chains (calculated as the sum of the contributions of the constituent amino acids), the absolute heat capacities of the N fragment and the unfolded complex are about 2 kJ x K(-1) x mol(-1) lower than the fully solvated-chain values. We attribute this discrepancy to burial of the apolar surface in the N fragment (as burial of the polar area is expected to lead to an increase in heat capacity). Illustrative calculations suggest that burial of about 1000--1600 A(2) of apolar surface takes place in the N fragment (probably accompanied by the burial of a smaller amount of polar surface). In general, this work is supportive of heat capacity measurements on protein fragments being useful as probes of surface burial in studies to characterize protein unfolded states and the high regions of protein folding landscapes.


Crystal structure of SARS-CoV-2 nsp10 bound to nsp14-ExoN domain reveals an exoribonuclease with both structural and functional integrity.
The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.


Role of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations-a meta-analysis.
The presence of distant metastasis is associated with an adverse outcome in papillary thyroid cancer. We performed a meta-analysis to investigate the role of molecular markers as predictors for distant metastasis in papillary thyroid cancer. Four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library were searched, and odds ratio and its 95% confidence interval concerning the association of BRAF, RAS, and TERT promoter mutations and RET/PTC rearrangements with distant metastasis were calculated using random-effects model. In total, 42 studies with 11,109 papillary thyroid cancers were included for meta-analyses. Overall, the presence of TERT promoter (odds ratio = 5.95; 95% confidence interval = 2.95-11.99), RAS mutations (odds ratio = 2.5; 95% confidence interval = 1.00-6.22), and RET/PTC rearrangements (odds ratio = 1.92; 95% confidence interval = 1.03-3.56) were found to be associated with a significantly increased risk for distant metastasis. BRAF mutations were not associated with an elevated risk for distant metastasis (odds ratio = 0.79; 95% confidence interval = 0.54-1.16). In conclusion, our study demonstrated the promising value of few molecular biomarkers, especially TERT promoter mutations in predicting distant metastasis in papillary thyroid cancers, while BRAF mutations showed no association with distant metastasis. Our study affirms the value of selected mutations for tumor risk stratification and assessment of patients' prognosis.


Cholesterol accessibility at the ciliary membrane controls hedgehog signaling.
Previously we proposed that transmission of the hedgehog signal across the plasma membrane by Smoothened is triggered by its interaction with cholesterol (Luchetti et al., 2016). But how is cholesterol, an abundant lipid, regulated tightly enough to control a signaling system that can cause birth defects and cancer? Using toxin-based sensors that distinguish between distinct pools of cholesterol, we find that Smoothened activation and Hedgehog signaling are driven by a biochemically-defined, small fraction of membrane cholesterol, termed accessible cholesterol. Increasing cholesterol accessibility by depletion of sphingomyelin, which sequesters cholesterol in complexes, amplifies Hedgehog signaling. Hedgehog ligands increase cholesterol accessibility in the membrane of the primary cilium by inactivating the transporter-like protein Patched 1. Trapping this accessible cholesterol blocks Hedgehog signal transmission across the membrane. Our work shows that the organization of cholesterol in the ciliary membrane can be modified by extracellular ligands to control the activity of cilia-localized signaling proteins.


Changes of gastric nitric oxide in neonatal rats with hypoxic-ischemic encephalopathy.
In order to study the changes of nitric oxide (NO) in gastric wall in hypoxic neonatal rats, the activity of nitric oxide synthase (NOS) of gastric wall was measured and the NADPH-diaphorase biochemistry test was taken to show the distribution of NOS in the gastric wall of neonatal rats. The results showed that compared with normal rats, NOS had no significant changes in the acute hypoxic rats (P > 0.05). However, in hypoxic-ischemic encephalopathy (HIE) neonatal rats, the activity of NOS was markedly increased (P < 0.01), and the NOS positive reactive products were markedly increased in the gastric muscle, but no changes in the mucosal and submucosal layers were observed. The results suggest that the decreased gastric motivation and the gastric mucosal lesions caused by asphyxia are associated with the changes of NO in gastric wall.


Social disparities in sleep health of African populations: A systematic review and meta-analysis of observational studies.
To document the relationship between socioeconomic status (SES) and sleep health in African populations. Observational cross-sectional or cohort studies examining the association between SES indicators and sleep outcomes in participants from African countries were included. The search was performed in the MEDLINE, Embase, and Web of Science Core Collection electronic databases in June 2021. Selection, confounding, attrition/exclusion, detection, and selective reporting bias were assessed using the OHAT Risk of Bias Tool. Random effects meta-analysis was used for summarizing the effect estimates. Forty-three reports were selected, having sampled 153,372 Africans from 26 countries. Education was the most frequent SES indicator and composite measures of sleep quality or disturbances was the most common sleep outcome. Low educational attainment was significantly associated with lower odds of short sleep (odds ratio [OR]=0.65, 95% confidence intervals [0.50, 0.84], p = .001) and higher odds of insomnia (OR=1.53, [1.18, 1.99], p = .001) or poor sleep quality (OR=1.60, [1.17, 2.18], p = .003). Low levels of income/assets were related to higher odds of insomnia (OR=1.38, [1.02, 1.86], p = .04) and low occupational/employment status was linked to lower odds of short sleep duration (OR=0.49, [0.30, 0.79], p = .004). Socioeconomic disadvantage was a significant predictor of insomnia and poor sleep quality, while it was associated with longer sleep duration. Significant heterogeneity in terms of exposure and outcomes, scarcity of longitudinal designs, lack of objective outcome measurement, and low representation of rural samples and participants from low-income countries limit the quality of evidence.


[H3-labeled cortisol metabolism in the renal, splenic and thymic cells of intact and adrenalectomized rats].
A study was made of the metabolism of 3H-cortisol in the kidney, spleen and thymus cytosol and microsomes of intact and adrenalectomized rats. Cortisone and tetrahydrocortisone were found to be the main cortisol metabolites in the kidney cytosol and microsomes in these two groups of animals. In intact rats, the tetrahydrocortisone level in the kidney cytosol was hizher than that in the microsome fraction. After adrenalectomy opposite changes were noted: the tetrahydrocortisone level was increased in the microsome fraction and significantly lowered in the cytosol which might be accounted for by a decreased rate of cortisol metabolism and a raised retention of tetrahydrocortisone by the endoplasmic reticulum membranes. Cortisone and tetrahydrocortisone turned out to be the main metabolites of cortisol the rat spleen and thymus cytosol but their content was much lower than that in the kidneys.


Surgical Management of Metastatic Disease.
Sarcomas are rare cancers of mesenchymal cell origin that include many histologic subtypes and molecularly distinct entities. For primary resectable sarcoma, surgery is the mainstay of treatment. Despite treatment, approximately 50% of patients with soft tissue sarcoma are diagnosed with or develop distant metastases, significantly affecting their survival. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in select patients who receive multimodality therapy, including surgery, for their metastatic disease. This article provides an overview of the literature on surgical management of pulmonary and hepatic sarcoma metastases.


5-Bromo-2-deoxyuridine regulates invasiveness and expression of integrins and matrix-degrading proteinases in a differentiated hamster melanoma cell.
Cell interactions with the extracellular matrix play a critical role in regulating complex processes such as terminal differentiation and tumor progression. In these studies we describe a melanoma cell system that should be useful in addressing the regulation of cell-matrix interactions and the roles they play in regulating differentiation and cell invasiveness. CS (suspension)-1 melanoma cells are relatively well differentiated: they are melanotic, responsive to melanocyte-stimulating hormone, and express TA99, a melanosome membrane differentiation marker. Their repertoire of integrin receptors for extracellular matrix ligands is limited; in particular, they lack receptors for vitronectin, accounting for the observation that they are nonadherent when cultured in the presence of serum. CS-1 cells are noninvasive as well, and express low levels of both metalloproteinases and activated plasminogen activators. Treatment of these cells with melanocyte-stimulating hormone causes them to increase melanin production and assume an arborized phenotype, suggesting that it promotes their further differentiation. In contrast, treatment of CS-1 with the thymidine analog 5-bromodeoxyuridine, converts them to a highly invasive cell population (termed BCS-1) that loses its differentiated properties and responsiveness to melanocyte-stimulating hormone, acquires a broad integrin repertoire (including vitronectin receptors), and expresses elevated levels of metalloproteinases and activated urokinase. From these observations and findings of others on BrdU treatment of other developmental lineages, we hypothesize that BrdU both suppresses differentiation and promotes invasiveness of CS-1 cells. The demonstrated manipulability of CS-1 cells should make them extremely useful for studying the regulation of both terminal differentiation and tumor progression in the melanocyte lineage.


Latitudinal environmental niches and riverine barriers shaped the phylogeography of the Central Chilean endemic Dioscorea humilis (Dioscoreaceae).
The effects of Pleistocene glaciations and geographical barriers on the phylogeographic patterns of lowland plant species in Mediterranean-climate areas of Central Chile are poorly understood. We used Dioscorea humilis (Dioscoreaceae), a dioecious geophyte extending 530 km from the Valparaíso to the Bío-Bío Regions, as a case study to disentangle the spatio-temporal evolution of populations in conjunction with latitudinal environmental changes since the Last Inter-Glacial (LIG) to the present. We used nuclear microsatellite loci, chloroplast (cpDNA) sequences and environmental niche modelling (ENM) to construct current and past scenarios from bioclimatic and geographical variables and to infer the evolutionary history of the taxa. We found strong genetic differentiation at nuclear microsatellite loci between the two subspecies of D. humilis, probably predating the LIG. Bayesian analyses of population structure revealed strong genetic differentiation of the widespread D. humilis subsp. humilis into northern and southern population groups, separated by the Maipo river. ENM revealed that the ecological niche differentiation of both groups have been maintained up to present times although their respective geographical distributions apparently fluctuated in concert with the climatic oscillations of the Last Glacial Maximum (LGM) and the Holocene. Genetic data revealed signatures of eastern and western postglacial expansion of the northern populations from the central Chilean depression, whereas the southern ones experienced a rapid southward expansion after the LGM. This study describes the complex evolutionary histories of lowland Mediterranean Chilean plants mediated by the summed effects of spatial isolation caused by riverine geographical barriers and the climatic changes of the Quaternary.


[The evaluation of 250 patients with thoracoabdominal injuries].
Prognostic factors affecting mortality and morbidity in thoracoabdominal injuries were evaluated. Two hundred and fifty patients (227 males, 23 females; mean age 30.1+/-5.11; range 15 to 71 years) who had been exposed to thoracoabdominal injuries and underwent laparotomy between June 1996 and November 2005 were investigated retrospectively. Patients were assessed according to age, sex, trauma-operation interval, shock, hospitalization period, number of injured organs, blood transfusion, timing of closed thorax drainage, thoracotomy, Abdominal Trauma Index, Injury Severity Score, Abbreviated Injury Score, Revised Trauma Score, and complications. Mortality and morbidity ratios were 15.6% and 53.5%, respectively. The factors effective on mortality were trauma-operation interval >or=3 hours (p=0.03), presence of shock (p=0.03), increase in the rate of blood transfusion (p=0.001), injured organ number >or=3 (p=0.001), and not performing early-term closed thorax drainage (p=0.005). Trauma-operation interval <3 (p=0.02), increase in the rate of blood transfusion (p=0.02), injured organ number >or=3 (p=0.001), and not performing early-term closed thorax drainage (p=0.005) were the factors effective on morbidity. It was determined that trauma-operation period >or=3 hours, number of injured organs >or=3, and increased number of blood transfusions increased both mortality and morbidity. However, presence of shock increased only mortality. On the other hand, application of closed thorax drainage within a reasonable time period was determined to decrease mortality and morbidity.


Crystal structure of Mycobacterium tuberculosis VapC20 toxin and its interactions with cognate antitoxin, VapB20, suggest a model for toxin-antitoxin assembly.
VapBCs, virulence-associated proteins, are the most abundant type II toxin-antitoxin (TA) systems in prokaryotes. Under normal conditions, toxin and antitoxin interact to form a heterooctameric complex, which upon binding to operator sites, inhibits their own expression. Under stress conditions, the VapB antitoxin is degraded by cellular proteases to release a free VapC toxin, which in turn inhibits cell growth mainly by targeting protein translation. However, the intermediate steps involved in the assembly of the heterooctameric complex have not been resolved. Here, we report a 1.75 Å resolution crystal structure of VapC20, a Sarcin-Ricin loop cleaving toxin from type II TA system of Mycobacterium tuberculosis. Using analytical ultracentrifugation (AUC) studies, we show that VapC20 exists as a homodimer in solution. The structural analysis of VapC homologs further suggests that VapCs form homodimers. We demonstrate that VapC20 is an obligate homodimer, and its self-association is critical for its folding and activity. Surface plasmon resonance experiments suggest that VapC20 interacts with its cognate antitoxin VapB20 to form a stable complex with nanomolar affinity. A high association rate coupled with a very slow dissociation rate ensures minimal toxicity under normal growth conditions. AUC studies reveal that VapB20 also exists as a homodimer in solution and further associates with VapC20 dimers to form heterotetramers and heterooctamers in a concentration-dependent manner. The results presented here provide valuable insights into the assembly of VapBC family of toxins which is essential for their function and regulation. Structural data are available in the PDB under the accession numbers 5WZF and 5WZ4.


Linear IgA disease: clinical presentation, diagnosis, and pathogenesis.
Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics.


Anastomotic Leakage and Chronic Presacral Sinus Formation After Low Anterior Resection: Results From a Large Cross-sectional Study.
Little is known about late detected anastomotic leakage after low anterior resection for rectal cancer, and the proportion of leakages that develops into a chronic presacral sinus. In this collaborative snapshot research project, data from registered rectal cancer resections in the Dutch Surgical Colorectal Audit in 2011 were extended with additional treatment and long-term outcome data. Independent predictors for anastomotic leakage were determined using a binary logistic model. A total of 71 out of the potential 94 hospitals participated. From the 2095 registered patients, 998 underwent a low anterior resection, of whom 88.8% received any form of neoadjuvant therapy. Median follow-up was 43 months (interquartile range 35-47). Anastomotic leakage was diagnosed in 13.4% within 30 days, which increased to 20.0% (200/998) beyond 30 days. Nonhealing of the leakage at 12 months was 48%, resulting in an overall proportion of chronic presacral sinus of 9.5%. Independent predictors for anastomotic leakage at any time during follow-up were neoadjuvant therapy (odds ratio 2.85; 95% confidence interval 1.00-8.11) and a distal (≤3 cm from the anorectal junction on magnetic resonance imaging) tumor location (odds ratio 1.88; 95% confidence interval 1.02-3.46). This cross-sectional study of low anterior resection for rectal cancer in the Netherlands in 2011, with almost routine use of neoadjuvant radiotherapy, shows that one third of anastomotic leakages is diagnosed beyond 30 days, and almost half of the leakages eventually do not heal. Chronic presacral sinus is a significant clinical problem that deserves more attention.


BET, FTIR, and RAMAN characterizations of activated carbon from waste oil fly ash.
Activated carbon (AC), a porous material with high pore volume, attracts increasing attention owing to its potential applications in several fields. The development of a porous structure in AC marginally relies on both the treatment methods and the type of precursor. Thus far, both renewable and nonrenewable precursor sources have been used to synthesize AC with high surface area and pore volume. This study presents the synthesis of AC via physicochemical treatment of waste oil fly ash (OFA), a waste material produced from power plants. The aim was to produce AC by adding surface pores and surface functional groups to the basal plane of OFA. Toward this objective, OFA was first chemically leached/activated with various combinations of H2SO4 and H3PO4, and then physically activated with CO2 at 900 °C. The chemical activation step, synergistically combined with CO2 activation, resulted in an increase of 24 times the specific surface area of the OFA. The maximum increase in surface area was obtained for the sample physicochemically treated with 100% H2SO4 . Moreover, the spectroscopic analysis confirmed the presence of acid functional groups after the chemical treatment step. To explore the surface heterogeneity, adsorptive potential distribution in terms of surface energy was also discussed as a function of the surface coverage. Following chemical activation, the OFA surface became heterogeneous. A major portion of the AC showed surface energy in the range of 40-50 erg/K, which was further increased as a result of physical activation at a higher temperature. Thus, the synergism created by physicochemical activation resulted in a material with high surface area and pore volume, and excellent adsorption characteristics. From the findings of this study, it was concluded that OFA is a cost-effective and environmentally benign precursor for the synthesis of AC.


Analysis of an endotracheal intubation service provided by respiratory care practitioners.
Our Respiratory Care Services Department provides an endotracheal intubation service that responds to all intubation requests. Intubation is performed by registered respiratory therapists who complete an 8-hour training program, advanced cardiac life support (ACLS) training and certification, and clinical performance of intubation with supervision. The goals of this service are (1) to provide competent persons for performing this service, (2) to assure a rapid response time, and (3) to be cost-effective. A retrospective analysis of our service was conducted over a 1-year period (7/90 to 6/91), and calculations were made of the intubation success rate and complication rate. Of the 833 total intubations, 791 were successfully performed by respiratory care practitioners; 730 of those successful intubations (92.3%) were accomplished in fewer than 3 attempts. Recognized complications occurred in 96 intubations (12.1%) and included oral bleeding, vomiting, and short periods of oxygen desaturation. In the 5.1% (42) of the patients not intubated by our service, 22 required heavy sedation, and an anesthesiologist was consulted; 17 patients were intubated by other physicians; and 3 tracheotomies were performed. Multiple intubation attempts were a result of secretions, induced bradycardia, blade-light malfunction, damaged cuff, and esophageal intubations. Respiratory Care Services can provide an effective intubation service. Cost savings were realized by centralizing equipment.


Diagnostic Performance of Decubitus Photon-Counting Detector CT Myelography for the Detection of CSF-Venous Fistulas.
CSF-venous fistulas are a common cause of spontaneous intracranial hypotension. Lateral decubitus digital subtraction myelography and CT myelography are the diagnostic imaging standards to identify these fistulas. Photon-counting CT myelography has technological advantages that might improve CSF-venous fistula detection, though no large studies have yet assessed its diagnostic performance. We sought to determine the diagnostic yield of photon-counting detector CT myelography for detection of CSF-venous fistulas in patients with spontaneous intracranial hypotension. We retrospectively searched our database for all decubitus photon-counting detector CT myelograms performed at our institution since the introduction of the technique in our practice. Per our institutional workflow, all patients had prior contrast-enhanced brain MR imaging and spine MR imaging showing no extradural CSF. Two neuroradiologists reviewed preprocedural brain MRIs, assessing previously described findings of intracranial hypotension (Bern score). Additionally, 2 different neuroradiologists assessed each myelogram for a definitive or equivocal CSF-venous fistula. The yield of photon-counting detector CT myelography was calculated and stratified by the Bern score using low-, intermediate-, and high-probability tiers. Fifty-seven consecutive photon-counting detector CT myelograms in 57 patients were included. A single CSF-venous fistula was definitively present in 38/57 patients. After we stratified by the Bern score, a definitive fistula was seen in 56.0%, 73.3%, and 76.5% of patients with low-, intermediate-, and high-probability brain MR imaging, respectively. Decubitus photon-counting detector CT myelography has an excellent diagnostic performance for the detection of CSF-venous fistulas. The yield for patients with intermediate- and high-probability Bern scores is at least as high as previously reported yields of decubitus digital subtraction myelography and CT myelography using energy-integrating detector scanners. The yield for patients with low-probability Bern scores appears to be greater compared with other modalities. Due to the retrospective nature of this study, future prospective work will be needed to compare the sensitivity of photon-counting detector CT myelography with other modalities.


Comorbidity on disorders with loss of impulse-control: pathological gambling, addictions and personality disorders.
To analyze the comorbidity of pathological gamblers, mainly in disorders with loss of impulse-control as addictions and personality disorders (PD). Also, to discuss addictive and impulsive characteristics of pathological gambling (PG), and their implications in prognosis and treatment. Cross-sectional study on 162 patients with PG admitted for treatment in a specific residential unit. The SCID-I and II were used for the addiction and the PD diagnosis. For the diagnosis and evaluation of PG the SOGS, AGQ III and the Gambling Severity Index were also used. The 61.1 % of the patients presented some PD, where the cluster B ones (impulsive group) were more frequent, followed by C and A ones. 63.3% of patients had had in their lives substance dependence criteria, where alcohol dependence was the most prevalent. The presence of PD is related to the gravity of the addiction by the dependence to more than one substance (chi2=7.15; p<0.008). TP and substance-related disorders (SRD) are frequent comorbidities of the PG. Their co-presentation could mean worse prognosis of this patients. The PG as impulsive disorder could help to the understanding of the etiopathogenia of this disorder, but also of the prognosis. This hypothesis will add to the addictive one other treatment approaches that should be included in future studies of PG.


Photon time-of-flight-assisted positron emission tomography.
In positron emission tomography (PET), the annihilation radiation is usually detected as a coincidence occurrence that localizes the position of the annihilation event to a straight line joining the detectors. The measure of the difference between the time of flight (TOF) of the annihilation photons between their inception and their detection permits the localization of the position of the annihilation event along the coincidence line. The incorporation of TOF information into the PET reconstruction process improves the signal-to-noise ratio in the image obtained. The utilization of scintillation detectors utilizing cesium fluoride scintillators, fast photomultiplier tubes, and fast timing circuits allows sub-nanosecond coincidence timing resolution needed for the effective use of TOF in PET. Mathematical considerations and pilot experiments show that with state-of-the-art electronic components and through the application of proper reconstruction algorithms, the combination of TOF and PET positional data improves severalfold the signal-to-noise ratio with respect to conventional PET image reconstruction at the cost of increasing the amount of data to be processed. The construction of a TOF-assisted PET device is within the capability of state-of-the-art technology.


Unintentional injuries among refugee and immigrant children and youth in Ontario, Canada: a population-based cross-sectional study.
Unintentional injuries are a leading reason for seeking emergency care. Refugees face vulnerabilities that may contribute to injury risk. We aimed to compare the rates of unintentional injuries in immigrant children and youth by visa class and region of origin. Population-based, cross-sectional study of children and youth (0-24 years) from immigrant families residing in Ontario, Canada, from 2011 to 2012. Multiple linked health and administrative databases were used to describe unintentional injuries by immigration visa class and region of origin. Poisson regression models estimated rate ratios for injuries. There were 6596.0 and 8122.3 emergency department visits per 100 000 non-refugee and refugee immigrants, respectively. Hospitalisation rates were 144.9 and 185.2 per 100 000 in each of these groups. The unintentional injury rate among refugees was 20% higher than among non-refugees (adjusted rate ratio (ARR) 1.20, 95% CI 1.16, 1.24). In both groups, rates were lowest among East and South Asians. Young age, male sex, and high income were associated with injury risk. Compared with non-refugees, refugees had higher rates of injury across most causes, including for motor vehicle injuries (ARR 1.51, 95% CI 1.40, 1.62), poisoning (ARR 1.40, 95% CI 1.26, 1.56) and suffocation (ARR 1.39, 95% CI 1.04, 1.84). The observed 20% higher rate of unintentional injuries among refugees compared with non-refugees highlights an important opportunity for targeting population-based public health and safety interventions. Engaging refugee families shortly after arrival in active efforts for injury prevention may reduce social vulnerabilities and cultural risk factors for injury in this population.


Neutralizing and enhancing activities of human respiratory syncytial virus-specific antibodies.
The neutralizing and enhancing activities of respiratory syncytial virus (RSV)-specific antibodies were examined. These two biological activities were measured for a panel of six monoclonal antibodies (MAbs) specific to the RSV surface F and G glycoproteins. Four MAbs specific for the F protein possessed both neutralizing and enhancing activities. One MAb (11-2-D2), specific to the G protein, enhanced RSV infection of U937 cells, a human macrophage cell line, but did not neutralize virus infectivity. One MAb (11-3-A3), specific to the F protein, efficiently neutralized virus infectivity but did not enhance RSV infection of U937 cells. MAb 11-3-A3 neutralized representative strains of the two antigenic subtypes of RSV. Assays performed with mixtures of MAbs showed that high concentrations of MAb 11-3-A3 masked the enhancing activity of MAb 11-2-D2. The assay of mixtures of two MAbs possessing only enhancing activities demonstrated that this response was synergistic. The role of neutralizing and enhancing antibodies in determining the outcome of RSV infection was examined for infants from whom cord blood serum samples were collected at birth. There was no significant difference in the magnitude of the serum-enhancing activities between infants who were hospitalized with RSV infections and a group of age- and sex-matched control infants with no reported respiratory illness requiring hospitalization. However, the results indicated a possible correlation between RSV infection of the infants and the occurrence of in vitro antibody-dependent enhancement of the cord blood sera at a serum dilution of 10(-2). A significant inverse correlation was found between the plaque-neutralizing and enhancing activities of the cord blood sera from infants, irrespective of subsequent RSV infection. These data are discussed in relation to the possible contribution of antibody-dependent enhancement to the normal course of RSV pathology in vivo.


Chronic recurrent multifocal osteomyelitis-case report of two patients and review of literature.
Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory skeletal disease characterized by unifocal or multifocal nonbacterial inflammatory bone lesions in the metaphysis of long bones. Common sites of CRMO are tibia, pelvis, proximal femur, clavicle, calcaneum and vertebrae. However, unifocal presentation or presentation in adults, atypical locations, and absence of recurrence have also been reported. We describe two cases of female patients with unifocal presentation of nonbacterial inflammatory bone lesions in the upper and lower extremity. Furthermore, a review of literature is presented. Although CRMO is seen primarily in children and adolescents, and usually occurs in a multifocal pattern, our cases illustrate that this disease can arise in adult patients and in a single location. The diagnosis of CRMO should be made in a multi-disciplinary approach amongst orthopedic surgeons, radiologists and pathologists.


Enhancing the Catalytic Performance of Group I, II Metal Halides in the Cycloaddition of CO2 to Epoxides under Atmospheric Conditions by Cooperation with Homogeneous and Heterogeneous Highly Nucleophilic Aminopyridines: Experimental and Theoretical Study.
Compared to metal-organic complexes and transition-metal halides, group I metal halides are attractive catalysts for the crucial cycloaddition reaction of CO2 to epoxides as they are ubiquitously available and inexpensive, have a low molecular weight, and are not based on (potentially) endangered metals, especially for the case of sodium and potassium. Nevertheless, given their low intrinsic catalytic efficiency, they require the assistance of additional catalytic moieties. In this work, we show that by exploiting the high nucleophilicity of opportunely designed aminopyridines, catalytic systems based on alkaline metals can be formed, which allow the cycloaddition of CO2 to epoxides to proceed under atmospheric pressure at moderate temperatures. Importantly, the aminopyridine nucleophiles can be applied in their heterogenized form, leading to a recyclable catalytic system. An investigation of the reaction mechanism by density functional theory calculations shows that metal halide complexes and nucleophilic pyridines can work as a dual cooperative catalytic system where the use of aminopyridines leads to lower energy barriers for the opening of the epoxide ring, and halide-adducts are involved in the subsequent steps of CO2 insertion and ring closure.


Static Laue diffraction studies on acetylcholinesterase.
Acetylcholinesterase (AChE) is one of nature's fastest enzymes, despite the fact that its three-dimensional structure reveals its active site to be deeply sequestered within the molecule. This raises questions with respect to traffic of substrate to, and products from, the active site, which may be investigated by time-resolved crystallography. In order to address one aspect of the feasibility of performing time-resolved studies on AChE, a data set has been collected using the Laue technique on a trigonal crystal of Torpedo californica AChE soaked with the reversible inhibitor edrophonium, using a total X-ray exposure time of 24 ms. Electron-density maps obtained from the Laue data, which are of surprisingly good quality compared with similar maps from monochromatic data, show essentially the same features. They clearly reveal the bound ligand, as well as a structural change in the conformation of the active-site Ser200 induced upon binding.


Intra-Abdominal Abscess and Primary Peritonitis Caused by Streptococcus anginosus.
The Streptococcus anginosus group of bacteria are low-virulence bacteria existing as commensals in the oral flora and gastrointestinal tracts of humans. S. anginosus may spread to the blood in individuals with poor oral hygiene in cases of oral infections, such as gingivitis and tooth abscesses, that develop following the loss of mucosal unity. This may lead to infections in the whole body, primarily as brain and liver abscesses. A 32-year-old male patient presented with complaints of nausea, vomiting, and diffuse abdominal pain. Diffuse abdominal tenderness and rebound tenderness were detected particularly in the epigastrium and right upper quadrant. Laboratory assessment revealed a leukocyte count of 20,500/mm(3). Free fluid around the liver and heterogeneous areas of abscess formation in the right lateral gallbladder were revealed on abdominal computed tomography. Diffuse adhesions between the bowel and seropurulent free liquid in the abdomen were detected on surgical exploration, and a sample was taken for cultures. The patient was discharged without complications on the sixth postoperative day and his antibiotic course was completed with 4 weeks of oral treatment. We reviewed the literature for similar cases of disseminated pyogenic infections caused by the S. anginosus group. It should be kept in mind that the oral flora bacterium S. anginosus may cause transient bacteremia and deep-seated organ abscesses in immunodeficient patients with poor oral hygiene. Such patients with intra-abdominal abscesses should be treated with antibiotics and surgery.


Using public control genotype data to increase power and decrease cost of case-control genetic association studies.
Genome-wide association (GWA) studies are a powerful approach for identifying novel genetic risk factors associated with human disease. A GWA study typically requires the inclusion of thousands of samples to have sufficient statistical power to detect single nucleotide polymorphisms that are associated with only modest increases in risk of disease given the heavy burden of a multiple test correction that is necessary to maintain valid statistical tests. Low statistical power and the high financial cost of performing a GWA study remains prohibitive for many scientific investigators anxious to perform such a study using their own samples. A number of remedies have been suggested to increase statistical power and decrease cost, including the utilization of free publicly available genotype data and multi-stage genotyping designs. Herein, we compare the statistical power and relative costs of alternative association study designs that use cases and screened controls to study designs that are based only on, or additionally include, free public control genotype data. We describe a novel replication-based two-stage study design, which uses free public control genotype data in the first stage and follow-up genotype data on case-matched controls in the second stage that preserves many of the advantages inherent when using only an epidemiologically matched set of controls. Specifically, we show that our proposed two-stage design can substantially increase statistical power and decrease cost of performing a GWA study while controlling the type-I error rate that can be inflated when using public controls due to differences in ancestry and batch genotype effects.


Nanoradiator-Mediated Deterministic Opto-Thermoelectric Manipulation.
Optical manipulation of colloidal nanoparticles and molecules is significant in numerous fields. Opto-thermoelectric nanotweezers exploiting multiple coupling among light, heat, and electric fields enables the low-power optical trapping of nanoparticles on a plasmonic substrate. However, the management of light-to-heat conversion for the versatile and precise manipulation of nanoparticles is still elusive. Herein, we explore the opto-thermoelectric trapping at plasmonic antennas that serve as optothermal nanoradiators to achieve the low-power (∼0.08 mW/μm2) and deterministic manipulation of nanoparticles. Specifically, precise optical manipulation of nanoparticles is achieved via optical control of the subwavelength thermal hot spots. We employ a femtosecond laser beam to further improve the heat localization and the precise trapping of single ∼30 nm semiconductor quantum dots at the antennas where the plasmon-exciton coupling can be tuned. With its low-power, precise, and versatile particle control, the opto-thermoelectric manipulation can have applications in photonics, life sciences, and colloidal sciences.


Relationship between the infarct localization and left ventricular rotation parameters following acute ST-segment elevation myocardial infarction.
This study was an investigation of the role of left ventricular (LV) apical rotation seen in the early period after myocardial infarction (MI) in predicting infarct localization. A total of 124 patients with a ST-Segment elevation myocardial infarction (STEMI) diagnosis who underwent primary percutaneous coronary intervention (PCI) and 50 healthy volunteers with similar demographic characteristics were included in the study. The relationship between 2-dimenstional speckle tracking echocardiography (STE)-guided LV apical rotation angle measurements and technetium-99m sestamibi-single-photon emission computed tomography (SPECT)-guided infarct localization was evaluated. Conventional echocardiography and STE were performed on average 2 days after PCI, and gated SPECT myocardial perfusion imaging (MPI) was performed within an average of 60 days. The apical rotation angle was lower in patients with an anterior MI compared with those who had an inferior MI and the control group (AntMI-InfMI: 6.51±2.4°, AntMI-Control: 13.20±2.5°, InfMI-Control: 14.3±2.1°; p value: 0.00, 0.00, 0.15, respectively). SPECT MPI analysis revealed the presence of an LV apical scar in all patients with acute anterior MI, but only 14 of those with inferior MI group (usually the inferoapical wall). The apical rotation angle recorded in patients with apical scar was lower than that of the patients without apical scar (7.6±2.8° and 14.5±2°, respectively; p=0.00). Receiver operating characteristic curve analysis yielded an area under the curve for apical rotation of 0.799 (p<0.01). The optimal cutoff value of 12.1° had a sensitivity of 78.3% and a specificity of 68.2% for predicting LV apical scar following STEMI. Detection of apical rotation angle decrease in the early period after STEMI may be useful in predicting extension of infarct scarring to the LV apex.


Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women.
Bacterial vaginosis (BV), the etiology of which is still uncertain, increases the risk of preterm birth. Recent PCR-based studies suggested that BV is associated with complex vaginal bacterial communities, including many newly recognized bacterial species in non-pregnant women. To examine whether these bacteria are also involved in BV in pregnant Japanese women, vaginal fluid samples were taken from 132 women, classified as normal (n = 98), intermediate (n = 21), or BV (n = 13) using the Nugent gram stain criteria, and studied. DNA extracted from these samples was analyzed for bacterial sequences of any Lactobacillus, four Lactobacillus species, and four BV-related bacteria by PCR with primers for 16S ribosomal DNA including a universal Lactobacillus primer, Lactobacillus species-specific primers for L. crispatus, L. jensenii, L. gasseri, and L. iners, and BV-related bacterium-specific primers for BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium. The prevalences of L. crispatus, L. jensenii, and L. gasseri were significantly higher, while those of BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium were significantly lower in the normal group than in the BV group. Unlike other Lactobacillus species, the prevalence of L. iners did not differ between the three groups and women with L. iners were significantly more likely to have BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium. Linear regression analysis revealed associations of BVAB2 and Megasphaera with Nugent score, and multivariate regression analyses suggested a close relationship between Eggerthella-like bacterium and BV. The BV-related bacteria, including BVAB2, Megasphaera, Leptotrichia, and Eggerthella-like bacterium, are common in the vagina of pregnant Japanese women with BV. The presence of L. iners may be correlated with vaginal colonization by these BV-related bacteria.


Low-Voltage Energy-Dispersive X-ray Microanalysis of Bulk Biological Materials.
: Low-voltage energy-dispersive X-ray microanalysis has a number of distinct advantages for measuring the concentration of light elements (Z = 11-20) in a largely organic matrix. Between 10 and 4 kV, there is a 50-fold decrease in the size of the incident beam-specimen interaction volume which enables discrete subcellular compartments to be analyzed. Experiments with mineral and organic samples of known chemical composition show that two of the most widely used analytical algorithms are capable of providing quantitative data at accelerating voltages as low as 5 kV. This technique is used at 5 kV to analyze frozen hydrated fracture faces of leaves of the tea plant which are known to contain aluminium. Higher levels of aluminium are found in the cell walls and are associated with increased levels of silicon and magnesium. The advantages and disadvantages of the experimental approach are discussed in relation to analysis carried out at higher voltages.


Single- versus 2-session Gamma Knife surgery for symptomatic midsize brain metastases: a propensity score-matched analysis.
Two-session Gamma Knife surgery (GKS) has recently been demonstrated to be an effective and less-invasive alternative for large brain metastases not treatable by microsurgical resection. This raises the clinical question of whether the 2-session GKS strategy further improves treatment outcomes for patients with symptomatic midsize brain metastases (2-10 cm3) as compared to single-session GKS. The present study aimed to compare the local therapeutic effects and toxicities of single-session and 2-session GKS for treating these lesions. Patients with focal neurological deficits attributable to midsize brain metastases who underwent upfront GKS during the period from 2010 to 2018 were retrospectively identified from an institutional database. Patients for whom both post-GKS imaging studies and neurological evaluations from outpatient visits were available were eligible. Using propensity score-matching (PSM) analysis, unique matched pairs which had a similar likelihood of receiving 2-session GKS were generated. The main outcome measure was a composite of imaging and/or neurological worsening of the lesion of interest. Functional improvement and overall survival (OS) were also compared between the 2 treatment arms. In total, 219 cancer patients with 252 symptomatic midsize brain metastases were eligible. Of these 252 tumors, 176 and 76 were treated with single- and 2-session GKS, respectively. After PSM, 68 pairs of tumors were obtained. The Gray test showed that 2-session GKS achieved a longer local progression-free interval than single-session GKS (1-year local control rate: 84% vs 53%; HR 0.31, 95% CI 0.16-0.63, p = 0.001). Two-session GKS was also associated with greater functional improvement in KPS scores (mean 18.3 ± 14.6 vs 12.8 ± 14.1, p = 0.040). The median OS did not differ significantly between single- and 2-session GKS (15.6 vs 24.7 months; HR 0.69, 95% CI 0.44-1.10, p = 0.11). Two-session GKS achieved more durable local tumor control and greater functional improvement than single-session GKS for patients with symptomatic midsize brain metastases, although there was no OS advantage.


Normal vs. disordered bereavement-related depression: are the differences real or tautological?
To evaluate whether the DSM distinction between uncomplicated (normal) and complicated (disordered) bereavement-related depression (BRD) has discriminant validity on a range of pathology indicators. The DSM's major depression bereavement exclusion (BE) excludes BRDs from diagnosis when they are uncomplicated (defined by brief duration, non-severe impairment, and lack of certain pathosuggestive symptoms) but classifies all other ("complicated") BRDs as major depression. A previous report seemed to support the uncomplicated/complicated distinction's discriminant validity. However, those arguing for eliminating the BE from DSM-5 dismiss the findings as 'tautological,' attributing the validator differences to definitional biases (e.g. 'uncomplicated' requires 'no suicidal ideation,' yet 'lifetime suicide attempt' was a validator). This study empirically tests whether the uncomplicated/complicated differences are real or tautological. Using National Comorbidity Survey data, confounds between definitional criteria for 'uncomplicated' and pathology validators were identified and corrected by deleting the biasing criteria and recalculating the corresponding validator's outcome. Six validators (interference with life, suicide attempt, melancholic depression, duration, hospitalization, and number of symptoms) were reanalyzed using unbiased definitions for 'uncomplicated.' All still yielded significantly lower pathology levels for uncomplicated BRDs, disconfirming the 'tautology' hypothesis. Regression analysis revealed that 'uncomplicated' offered incremental validity over severity alone in predicting pathology, so 'uncomplicated' cannot be equated with 'mild.' Uncomplicated BRDs' lower pathology validator levels are because of real syndromal differences, not definitional tautologies, supporting the BE's validity.


Family Meals and Adolescent Emotional Well-Being: Findings From a National Study.
To describe the relationship between family meals and adolescent mental health and determine whether the relationship differs by sex. Secondary analyses of a cross-sectional survey. A total of 8,500 nationally representative students. Reynolds Adolescent Depression Scale; Strengths and Difficulties Questionnaire; World Health Organization Well-being Index. Multiple regression models determined the relationships between family meals and mental health indicators; sociodemographic variables and family connection were included as covariates. Approximately 60% of adolescents shared family meals ≥5 times in the previous week, whereas 22% reported that they shared ≤2 meals in the previous week. Greater frequency of family meals was associated with fewer depressive symptoms (P < .001), fewer emotional difficulties (P < .001) and better emotional well-being (<.001). These relationships between family meals and depressive symptoms were attenuated by sex; the relationship was stronger for females than for males. Frequent family meals may have a protective effect on the mental health of adolescents, particularly for depressive symptoms in girls. Interventions that aim to increase the frequency of family meals are needed to evaluate whether family meals alone can have an emotional benefit for adolescents.


The problem of attrition in a Finnish longitudinal survey on depression.
A cohort of all school children aged 16 years in 1983 (n = 2194, 96.7%) in Tampere, Finland were studied at 16, 22 and 32 years of age by self-reported questionnaires. The non-response pattern was considered by modelling the individual response probability by panel year and gender. Gender and school performance at age 16 years were the most important predictors of non-response. They explained away the effect of all other variables at 16 and 22 years, except for earlier non-response at age 22. However, the ability of the models to predict non-respondents was very poor. The effect of attrition for the estimation of depression prevalence was evaluated first by longitudinal weighting methods used commonly in survey studies and then by Markov chain Monte Carlo (MCMC) simulation of the missing depression status. Under the missing-at-random assumption (MAR), both applied correction methods gave estimates of roughly the same size and did not significantly differ from the observed prevalence of depression. No indication of informative missingness was found. We therefore conclude that attrition does not seriously bias the estimation of depression prevalence in the data. In general, non-response models, which are needed to correct for informative missingness, are likely to have poor ability to predict non-response. Therefore, the plausibility of the MAR assumption is important in the presence of attrition.


A rheological study of packed red blood cell suspensions with an oscillating ball microrheometer.
Rheological properties of concentrated red blood cell suspensions are studied with a magneto acoustic microrheometer in which a ball is suspended in a vertically oriented cylindrical tube. The rheometer uses a conventional falling ball technique to measure steady state viscosity and a vertically oscillating, magnetically driven ball for viscoelastic measurements. The motion of the ball is tracked by ultrasound echo location in which sound waves are transmitted and received by an ultrasound transducer mounted at the base of the tube. The compact size of the rheometer allows rheological studies to be made with microliter quantities of opaque suspensions and permits sudden and accurate changes in temperature. Also, values for the adiabatic compressibility are evaluated from measurements of the speed of sound.


Hippocampal neural cell degeneration and memory deficit in high-fat diet-induced postnatal obese rats- exploring the comparable benefits of choline and DHA or environmental enrichment.
Childhood obesity increases risk for neural dysfunctions causing learning and memory deficits. The objective of the study is to identify the effects of high fat diet-induced obesity in postnatal period on serum lipids, memory and neural cell survival in hippocampus and compare the role of choline and DHA or environmental enrichment in attenuating the alterations. 21 day postnatal male Sprague Dawley rats were assigned as Normal control [NC] fed normal chow diet, Obesity-induced [OB] fed high fat diet, Obesity-induced fed choline & DHA [OB + CHO + DHA], Obesity-induced environmental enrichment [OB + EE] [n = 8/group]. Memory was assessed using radial arm maze. Subsequently blood was collected for serum lipid analysis and rats were euthanized. 5 µm hippocampal sections were processed for cresyl-violet stain. Surviving neural cells were counted using 100 µm scale. Memory errors were significantly higher [p < 0.001, 0.01] in OB compared to same in NC rats. Mean number of surviving neural cells in hippocampus of OB was significantly lesser [p < 0.01] compared to same in NC. Interventions in OB + CHO + DHA and OB + EE significantly attenuated [p < 0.01] memory errors and number of surviving neural cells in hippocampus [CA1, CA3 and DG] compared to same in OB. Moreover, hippocampal neural cell survival was found to be inversely related to serum lipid profile in OB group and was attenuated in OB + CHO + DHA and OB + EE rats. High fat diet-induced postnatal obesity in rats causes CA1/CA3 hippocampal neuro-degeneration and memory deficits. Supplementation of choline and DHA in obese rats attenuates these deficits.


The comparison of femoral curves and curves of contemporary intramedullary nails.
The aim of this study was to evaluate both the cortical and the medullary anterior bowing of the femur, and to compare these measurements with current intramedullary nails to assess the adequacy of their design. Lateral digital radiographic views of left femurs of 104 normal subjects (18-68 years old) were obtained. Radii of cortical and medullary curvatures of femurs were calculated using these images. The values obtained were compared to the radius of curvatures of ten different intramedullary nails. Medullary bowing was between 114 and 1,389 mm (mean: 722 mm, SD: 230 mm) and the cortical bowing was between 109 and 1,666 mm (mean: 770 mm, SD: 267 mm). For males, these values were 114-1,389 mm (mean: 722 mm, SD: 230 mm) and 109-1,666 mm (mean: 770 mm, SD: 267 mm), respectively. For females, they were 114-1,389 mm (mean: 722 mm, SD: 230 mm) and 109-1,666 mm (mean: 770 mm, SD: 267 mm), respectively. The differences between genders were not significant. Cortical and medullar bowing was strongly correlated with age (r=-0.269, p<0.006 and r=-0.234, p<0.017, respectively). These significances were produced by females only. Radii of curvatures of intramedullary nails ranged between 150 and 300 cm and were higher than the mean cortical (77 cm) and medullary (72.2 cm) bowings. The difference between the curves of femur and the contemporary femoral nails implicates the inadequacy of the design of such nails for the Caucasian race living in Anatolia. Therefore, such nails should be revised accordingly to prevent the above-mentioned complications.


Clinical outcomes of a diagnostic and treatment protocol in allergy/sensitivity patients.
This level II outcome study was conducted to examine the efficacy and toxicity of a diagnostic and treatment protocol using electrodermal screening (EDS) in allergy/sensitivity patients. Ninety-six patients with a diagnosis of allergy or sensitivity entered the study between 1994 and 1998; 90 participants completed the study. All participants followed the same protocol, and all interactions were with a single clinician at a single site. The Allergy Symptom Severity Index (ASSI) was developed to record symptomatic information. EDS - conductance measurement 1/( - of specific acupuncture points was used as an objective endpoint (indicator of outcome) and for identification of antigens, according to Voll criteria. All measurements were taken before and after treatment, and EDS was carried out at all treatment sessions. Outcome criteria suggesting efficacy were reduction in ASSI score, reduction in number of items testing positive, and normalization of conductance measurements. A statistical analysis of the outcomes was performed using the student's paired t-test. There was a statistically significant change in pre- and post-treatment measurements of the ASSI. The conductance measurements normalized and the number of items testing positive decreased compared to pre-treatment testing. In addition to these parameters, 87.2 percent of subjects rated efficacy as good to excellent, and less than one-percent rated the outcome as poor. The outcome demonstrated longevity, meaning that people who had their post-treatment evaluation up to three years after primary treatment were still showing minimal ASSI scores, with no additional treatment. The treatment appeared to work equally well across age groups and gender. Forty-eight percent of participants had an aggravation of symptoms after treatment, lasting an average of 10 hours, with reactions described as mild to moderate. Average cost of the desensitization protocol (all costs included) was $822.16. This protocol demonstrated efficacy without serious toxicity and no long-term adverse effects. It is natural, non-invasive, and does not require long periods of avoidance of offending foods or environmental stimuli. The desensitization protocol is a low-cost, effective therapy for the treatment of patients suffering from symptoms of allergy/sensitivity disease.